Approximately 0.7 to 1.7 million health care-associated infections (HAIs) occur in the U.S. each year in inpatients receiving care in U.S. acute care community-hospital stays. Many of these infections are caused by antibiotic resistant organisms including multidrug resistant gram-negative organisms (MDRGNOs). One of the prime predictors of morbidity and mortality following infection with drug resistant organisms is inadequate empiric and definitive antibiotic treatment of the infection. Lack of specific clinical practice guidelines for treatment of these organisms increases the ambiguity of effective treatment strategies. It is unclear what treatment regimens are being used within VA for treatment of MDRGNOs nor how effective they are. Therefore, the goal of this study is to use national VA data to describe current treatment strategies for select MDRGNOs (Carbapenem Resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, and Acinetobacter species) and the comparative effectiveness of these strategies on outcomes in Veterans. This study is highly relevant to patients seeking care in VA, as Veterans experience many of the risk factors associated with development of an MDRGNO infection. VA treats patients with serious complex conditions that require frequent hospitalization or contact with health care or use of invasive devices (i.e. spinal cord injury, amputations) that put them at risk for infections. MDRGNOS and inadequate treatment have a significant impact on morbidity and mortality outcomes in those with complex conditions. Also, the proposed research is related to the VA's Multidrug Resistant Organism (MDRO) Program that has developed and implemented national programs to reduce the transmission and spread of MRSA and Clostridium difficile. Our findings will produce effectiveness data on outcomes for MDRGNOs including CRE in a diverse population of Veterans that can be used by VA program offices for developing guidance for treatment. This research is innovative in that it will be the first study, to our knowledge, utilizing national VA microbiology, pharmacy, and medical encounter databases to answer comparative effectiveness research questions on effective treatment strategies for MDRGNOs. The long-term goal will be to develop actionable findings for decision makers that can be implemented to improve the effectiveness of treatment and healthcare of patients with MDRGNO infections across different populations.